This invention relates to a method and apparatus for analyzing solutes in a sample solution by nebulizing the solution and detecting the solute in the nebulized particles. More particularly, this invention relates to the use of a nebulizer which utilizes ultrasonic excitation to form a standing wave on a liquid surface. The particle size distribution of the nebulized liquid is relatively insensitive to liquid density and liquid surface tension.
At the present time apparatus are available for nebulizing a sample solution such as a liquid stream effluent from a liquid chromatography separation step and subsequently analyzing the nebulized liquid such as by mass spectrometry. Presently available means for analyzing small sample solutions include infrared spectroscopy and mass spectrometry. In electron impact mass spectrometry procedures, for example, the mass spectra of a sample is generated by ionizing the sample, determining the mass spectrum of the ionized sample and comparing the generated mass spectrum with reference mass spectra to determine the identity of the sample. In order to promote accuracy of the procedure, only the mass spectrum of one species should be generated at a given time.
In a liquid chromatograph, a stream of solvent, containing a mixture of chemical species in solution, is passed at elevated pressure through a chromatographic column. The column is so designed that it separates the mixture, by differential retention on the column, into its component species. The different species then emerge from the column as distinct bands in the solvent stream, separated in time. The liquid chromatograph provides therefore, an ideal device for the introduction into a mass spectrometer of single species, separated from initially complex mixtures.
In order for the species emerging from the column to be introduced into a mass spectrometer, removal of solvent from the dissolved species is desirable. The allows the ionization chamber of the mass spectrometer to operate at normal operating pressures (e.g., 10.sup.-5 to 10.sup.-6 torr for electron impact ionization; 1 torr for chemical ionization) and it allows normal ionization modes, such as electron or chemical to be used. Without efficient solvent removal from the species entering the ionization chamber of the mass spectrometer, hybrid and less well characterized mass spectra are produced.
In many systems for interfacing a liquid chromatograph to mass spectrometers, it is necessary to generate aerosols from the liquid chromatography liquid effluent to produce liquid particles having a relatively uniform size and within a count mean diameter of between about 5 and 30 microns. If the particles are to small, it is difficult to separate the solid particles produced therefrom after the solvent evaporates from the vaporous solvent. If the particles are too large, the solvent is incompletely evaporated and the force of gravity will divert them from their intended path. The count mean diameter is defined as the particle size within the aerosol for which half the total number of aerosol particles is larger and the other half is smaller.
An additional problem in forming aerosols from the effluent stream from a liquid chromatography (LC) process is that the LC process must be capable of accommodating a wide variety of solvents so that a wide variety of solutes having different solubility characteristics can be processed. These solvents have different density and surface tension characteristics which affect liquid particle size of an aerosol formed under a given set of energy conditions.
It has been proposed in U.S. Pat. Nos. 4,629.478; 4,687,929 and 4,762,995 to utilize a nebulizer for producing aerosol particles from an LC column for subsequent introduction into a mass spectrometer. The nebulizer forms liquid particles from a jet of liquid issuing from a nozzle orifice. The diameter of the orifice and the velocity of the jet are controlled so that the jet breaks up into monodisperse liquid particles. Unfortunately, the performance of this nebulizer is dependent upon the density, viscosity and surface tension characteristics of the liquid jet and it is difficult to produce consistently monodisperse aerosols from the variety of solvents utilized in LC. These nebulizers are unstable and require frequent adjustment. An alternative system is disclosed in U.S. Pat. No. 4,383,171 , although no specific nebulizer is disclosed.
An alternative means for forming aerosols from an LC effluent stream is disclosed in UK Patent Application 2,203,241A which utilizes a capillary tube to form a liquid jet in combination with heating means to heat liquid particles formed from the jet in order to vaporize the solvent in the particles.
Nebulizer devices also are utilized to form aerosols in a wide variety of applications, particularly in applications where liquid fuels are to be burned. It is more efficient to form aerosols from the liquid fuel to increase the surface area of the fuel so as to effect more complete combination. Generally, these nebulizers are utilized with a petroleum fraction having relatively uniform density and surface tension characteristics. Examples of such nebulizers are disclosed in U.S. Pat. Nos. 4,153,201; 4,352,459 and 4,723,708.
As disclosed in U.S. Pat. No. 4,980,057 and in the 38th ASMS Conference on Mass Spectrometry and Allied Products, pages 1222-1223, a system is provided for analyzing sample solutions comprising an ultrasonic nebulizer and a mass spectrometer. According to this patent, the desolvation chamber adjacent the nebulizer must be operated at subatmospheric pressures. Such operation causes "bumping" or surging of solvent which can disrupt the nebulizer operation. In order to eliminate "bumping", the liquid sample is introduced into the nebulizer orthogonally to the tip of the ultrasonic horn in the nebulizer and orthogonally to a helium stream which is introduced axially into the nebulizer through an axial conduit within the ultrasonic horn. Thus, the helium stream is positioned within the liquid sample stream and the liquid sample stream is fractured to form an aerosol by a combination of pneumatic and ultrasonic forces. In this system the liquid sample effluent conduit must be accurately aligned relative to the ultrasonic horn in contrast to introducing the liquid axially through the ultrasonic horn where proper alignment is inherent. During use, the liquid sample effluent conduit will become misaligned which requires periodic adjustment of the conduit's position. In addition, the use of a gas stream to intimately mix with the liquid sample stream rather than enclosing the liquid sample stream is undesirable since this mode of operation increases the probability that the liquid particles will impact with the apparatus wall and will be lost from downstream analysis.
Electron impact ionization is utilized in analytical processes to permit analysis of molecules dissolved in a liquid of varying composition by providing electron impact ionization spectra of the molecules. This is the fundamental goal of all "particle beam" interfaces for coupling liquid streams to mass spectrometers. The primary advantage of such spectra for the analysis or identification of small molecules (less than 1000 Daltons) is that they are highly specific to the molecules from which they are generated and provide a wealth of structural information. In addition, large libraries of such spectra exist such that it is possible to computer search for a match between the spectrum of an unknown compound and spectra in these libraries. These are the same kind of spectra that are produced by traditional coupling of a gas chromatograph to a mass spectrometer. Such spectra are the only kind widely accepted today for the analysis and identification of unknown compounds.
The specificity of such electron impact ionization spectra is a consequence of the fact that ionization occurs at a low pressure (typically less than 10.sup.-4 Torr) and that ionization of an individual molecule results solely from the collision of an energetic electron (energies typically 100-150 eV) with that neutral molecule.
It would be desirable to provide a system for forming an aerosol from the liquid effluent of an LC apparatus, regardless of solvent used in the stream. This would substantially eliminate the need for adjustment of the nebulizer when the LC stream solvent is changed. Such a system would be capable of producing aerosols having a relatively uniform droplet distribution, which in turn could be efficiently desolvated to produce a dry "particle beam" of any solute molecules dissolved in the LC solvent stream such that the electron impact ionization spectra of said solute molecules could be easily and efficiently generated.